Bioprospecting Research Group, School of Engineering, Universidad de La Sabana, Chía 250001, Colombia.
Bioorganic Chemistry Laboratory, Universidad Militar Nueva Granada, Cajicá 250247, Colombia.
Molecules. 2022 Jun 22;27(13):3996. doi: 10.3390/molecules27133996.
Genista monspessulana (L.) L.A.S. Johnson (Fabaceae) is a Mediterranean plant introduced to South America and other regions for ornamental purposes. However, it is considered an invasive shrub due to its reproductive vigor in many areas. Unlike other Genista plants, G. monspessulana has few studies disclosing its biologically active components, particularly cytotoxic agents against cancer cells. Thus, as part of our research on anti-proliferative bioactives, a set of ethanolic seed extracts from ten accessions of G. monspessulana, collected in the Bogotá plateau, were evaluated against four cell lines: PC-3 (prostate adenocarcinoma), SiHa (cervical carcinoma), A549 (lung carcinoma), and L929 (normal mouse fibroblasts). Extracts were also analyzed through liquid chromatography coupled with mass spectrometry (LC/MS) to record chemical fingerprints and determine the composition and metabolite variability between accessions. Using multiple covariate statistics, chemical and bioactivity datasets were integrated to recognize patterns and identify bioactive compounds among studied extracts. G. monspessulana seed-derived extracts exhibited dose-dependent antiproliferative activity on PC-3 and SiHa cell lines (>500 µg/mL < IC50 < 26.3 µg/mL). Seven compounds (1−7) were inferred as the compounds most likely responsible for the observed anti-proliferative activity and subsequently isolated and identified by spectroscopic techniques. A tricyclic quinolizidine (1) and a pyranoisoflavone (2) were found to be the most active compounds, exhibiting selectivity against PC-3 cell lines (IC50 < 18.6 µM). These compounds were used as precursors to obtain a quinolizidine-pyranoisoflavone adduct via Betti reaction, improving the activity against PC-3 and comparable to curcumin as the positive control. Results indicated that this composition−activity associative approach is advantageous to finding those bioactive principles efficiently within active extracts. This correlative association can be employed in further studies focused on the targeted isolation of anti-proliferative compounds from Genista plants and accessions.
蒙氏金雀花（L.）L.A.S.约翰逊（豆科）是一种地中海植物，因其观赏价值而被引入南美洲和其他地区。然而，由于其在许多地区具有很强的繁殖能力，它被认为是一种入侵灌木。与其他金雀花植物不同，蒙氏金雀花的生物活性成分，特别是对癌细胞的细胞毒性剂，研究较少。因此，作为我们对增殖抑制生物活性物质研究的一部分，对来自在波哥大高原收集的十个蒙氏金雀花品种的一组乙醇种子提取物进行了评估，这些提取物针对四种细胞系进行了评估：PC-3（前列腺腺癌）、SiHa（宫颈癌）、A549（肺癌）和 L929（正常小鼠成纤维细胞）。还通过液相色谱与质谱联用（LC/MS）对提取物进行了分析，以记录化学指纹图谱，并确定品种间的组成和代谢物变异性。使用多协变量统计，将化学和生物活性数据集整合在一起，以识别模式并确定研究提取物中的生物活性化合物。蒙氏金雀花种子衍生的提取物对 PC-3 和 SiHa 细胞系表现出剂量依赖性的增殖抑制活性（>500μg/mL<IC50<26.3μg/mL）。推断出七种化合物（1-7）是导致观察到的增殖抑制活性的最可能的化合物，并通过光谱技术进行了分离和鉴定。发现三环喹诺里定（1）和吡喃异黄酮（2）是最活跃的化合物，对 PC-3 细胞系具有选择性（IC50<18.6μM）。这些化合物被用作前体，通过 BETTI 反应获得喹诺里定-吡喃异黄酮加合物，提高了对 PC-3 的活性，与阳性对照姜黄素相当。结果表明，这种成分-活性关联方法有利于在活性提取物中有效地找到这些生物活性原理。这种关联可以用于进一步的研究，重点是从金雀花植物和品种中靶向分离增殖抑制化合物。
